Hepatotoxicity of silica nanoparticles with a diameter of 100 nm.

Nanomaterials have potential toxicity that is not found in micromaterials, and it is therefore essential to understand their biological activity and potential toxicity. We focused on silica nanoparticles, since it was previously reported that the intravenous administration of silica nanoparticles with a diameter of 70 nm (SP70) causes hepatic injury. In the present study, we focused on the effects of the particle diameter of silica. We found that silica nanoparticles caused acute liver toxicity at a diameter of 100 nm, and that liver sinusoidal endothelial cells are directly involved in silica nanoparticle-induced liver injury. These findings suggest that the diameter of nanoparticles has great influence on silica nanoparticle-induced liver injury.

Effect of surface charge on nano-sized silica particles-induced liver injury.

Nanomaterials are used frequently in microelectronics, cosmetics and sunscreen, and research for the development of nanomaterial-based drug delivery systems is promising. We previously reported that the intravenous administration of unmodified silica particles with a diameter of 70 nm (SP70) caused hepatic injury. Here, we examined the acute hepatic toxicity of SP70 modified with amino group (SP70-N) or carboxyl group (SP70-C). When administered intravenously into mice, SP70-N and SP70-C dose-dependently increased the serum level of alanine aminotransferase (ALT). However, the toxicity levels of surface charge-modified silica particles were much less weaker than the level of unmodified particles. When SP70 was repeatedly administered at 40 mg/kg twice a week for 4 weeks into mice, the hydroxyproline content of the liver significantly increased. Azan staining of the liver section indicated the extensive fibrosis. To the contrary, the repeated administration of SP70-N or SP70-C at 60 mg/kg twice a week for 4 weeks into mice did not cause the hepatic fibrosis. These findings suggest that the surface charge of nanomaterials could change their toxicity.

Effect of 70-nm silica particles on the toxicity of acetaminophen, tetracycline, trazodone, and 5-aminosalicylic acid in mice.

Exposure to nano-sized particles is increasing because they are used in a wide variety of industrial products, cosmetics, and pharmaceuticals. Some animal studies indicate that such nanomaterials may have some toxicity, but their synergistic actions on the adverse effects of drugs are not well understood. In this study, we investigated whether 70-nm silica particles (nSP70), which are widely used in cosmetics and drug delivery, affect the toxicity of a drug for inflammatory bowel disease (5-aminosalicylic acid), an antibiotic drug (tetracycline), an antidepressant drug (trazodone), and an antipyretic drug (acetaminophen) in mice. Co-administration of nSP70 with trazodone did not increase a biochemical marker of liver injury. In contrast, co-administration increased the hepatotoxicity of the other drugs. Co-administration of nSP70 and tetracycline was lethal. These findings indicate that evaluation of synergistic adverse effects is important for the application of nano-sized materials.